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Some lens opacities result from abnormal crystallins formed by mutations in the CRYBB2 gene.
Some lens opacities result from abnormal crystallins formed by mutations in the CRYBB2 gene.

Cataracts, Congenital Cerulean

Clinical Characteristics

Ocular Features

Lens opacities of tiny blue or white color generally appear from birth through 18 and 24 months of age but may not be diagnosed until adulthood.  They first appear at the outer age of the fetal lens nucleus or in more superficial cortical layers depending on the type.  Infants seem can be asymptomatic but may also be visually impaired from birth and develop nystagmus and amblyopia.  The opacities are usually bilateral and progressive.  Lens removal may be required in early infancy but often not until the 2nd to 4th decades.

Systemic Features

No systemic abnormalities are associated with cerulean cataracts.

Genetics

Lens opacities can, of course, be associated with chromosomal aberrations, developmental conditions, intrauterine infections, and metabolic errors as well as single gene mutations.   About 23% are familial but even among these there is considerable genetic and clinical heterogeneity that confounds the nosology despite notable recent progress in genotyping.  Due to clinical heterogeneity, it is not always possible to classify specific families based on the appearance and natural history of the lens opacities alone.

Cerulean cataracts of congenital or childhood onset can be due to mutations in genes that encode various lens crystallins.  Type 1 (CCA1; 115660) or ‘blue dot’ cerulean cataracts result from mutations in a gene located at 17q24 but its identity is as yet unknown. Intriguingly, it is located in the same chromosomal vicinity as the galactokinase deficiency gene (GALK1).  The lens opacities are inherited as an autosomal dominant. This gene, however, does not appear to code for any of the major structural proteins of the lens.

Type 2 (CCA2; 601547) results from mutations in the CRYBB2 gene (22q11.2-q12.2) encoding the beta-B2-crystallin protein.  Inheritance is autosomal dominant.

Type 3 (CCA3; 608983) is caused by mutations in CRYGD (2q33-q35) coding gamma-D-crystallin.  It has been reported in a single family in which it seemed to appear earlier and progress more rapidly than other types.  The pedigree pattern was consistent with autosomal dominant inheritance.  Mutations in the same gene also cause an allelic disorder designated nonnuclear polymorphic congenital cataracts or PCC (601286), which may simply be clinical heterogeneity of the same condition.

Type 4 (CCA4; 610202) is due to mutations in the MAF gene (16q22-q23) and is also inherited in an autosomal dominant pattern.  Lens opacities have a later, more juvenile onset and the lens opacities are located in a lamellar distribution in superficial cortical layers.  These are progressive and often result in posterior subcapsular opacification that requires lens extraction in adults.

Type 5 (CCA5) is the result of a mutation in a locus at 12q24 and is dominantly inherited.

Other forms of autosomal dominantly inherited, congenital, progressive lens opacities include Volkmann type (115665), Coppock-like (604307), lamellar (116800), and congenital posterior polar (116600) cataracts. 

Treatment Options

No treatment is known to prevent the opacities but serial evaluations and cataract surgery are required to prevent amblyopia as the opacities progress.

References

Berry V, Ionides AC, Moore AT, Bhattacharya SS. A novel locus for autosomal dominant congenital cerulean cataract maps to chromosome 12q. Eur J Hum Genet. 2011 Jul 6. doi: 10.1038/ejhg.2011.130.

PubMed ID: 
21731060

Plotnikova OV, Kondrashov FA, Vlasov PK, Grigorenko AP, Ginter EK, Rogaev EI. Conversion and compensatory evolution of the gamma-crystallin genes and identification of a cataractogenic mutation that reverses the sequence of the human CRYGD gene to an ancestral state. Am J Hum Genet. 2007 Jul;81(1):32-43.

PubMed ID: 
17564961

Hejtmancik JF. The genetics of cataract: our vision becomes clearer. Am J Hum Genet. 1998 Mar;62(3):520-5.

PubMed ID: 
9497271

Armitage MM, Kivlin JD, Ferrell RE. A progressive early onset cataract gene maps to human chromosome 17q24. Nat Genet. 1995 Jan;9(1):37-40.

PubMed ID: 
7704021